The studies proposed in this application will further investigate the role of cyclin D1 in hepatocyte proliferation, growth, metabolism and gene regulation. Cyclin D1 is a pivotal cell cycle control protein and an important oncogene that is over-expressed in many human cancers. Our previous studies have demonstrated that cyclin D1 plays a key role in hepatocyte proliferation. The studies outlined here will further define the mechanisms underlying the role of cyclin D1 in cell cycle progression, growth, and novel functions uncovered in our laboratory - the regulation of hepatic metabolism and the control of mRNA stability. We will define the role of functional domains of cyclin D1 in each of these processes. Our approach will involve the extensive use of transfection techniques and transgenic mice, and are intended to provide a significant advance in our understanding of the role of cyclin D1 in vivo. We expect that these studies will be highly relevant to the processes of liver regeneration, hepatic metabolism, and carcinogenesis. PUBLIC HEALTH RELEVANCE: This proposal examines the cellular actions of cyclin D1, a critical cell cycle control protein that plays a role in many human cancers. These studies will provide a better understanding of mechanisms that control liver regeneration and contribute to the development of cancer. This data will help to define potential targets for therapies for liver diseases and cancer.